We have receantly discovered that substitution of two fluorine atoms at C-10 of prostacyclin, not only achieves the expected stabilization of the molecule to acid hydrolysis but also serves to maintain both qualitatively and quantitatively the biological spectrum of natural prostacyclin. This "difluoro principle" has been tested in the case of TXA2, the only member of the arachidonate cascade which, because of its great instability (half-life ca 30 sec) has resisted chemical synthesis. The test has involved synthesis of the bicyclic difluorooxetane-oxane system attached to a cyclohexane ring (2). This compound turned out to be stable to .5N HC1. The stability of this system has encouraged us to proceed with the total synthesis of difluoro-TXA2 itself. The availability of this stable compound , in which the geometry of TXA2 is preserved would be of considerable importance as a mimic of TXA2 as well as provide the base for chemical operations directed to the synthesis of receptor antogonists and synthesis inhibitors of TXA2. At the same time we have initiated a program of synthesis of difluorinated arachidonic acids in which select methylene groups contiguous to the four double bonds are replaced by CF2. These substances will be employed as substrates for the cyclooxygenase as well as for the 5- and 12-lipoxygenases. Depending on the location of the CF2 grouping one would expect formation of the corresponding difluoroprostaglandins or difluoroleukotrienes, or observe ihibition of the respective enzymes. Inhibitors of this type may possess high selectivity for the cyclooxygenase and/or lipoxygenase pathways.